Substituted piperidine as a novel lead molecule for the treatment of Parkinson's disease: Synthesis, crystal structure, hirshfeld surface analysis, and molecular modeling

Khan B. A., Rehman O. U., Alsfouk A. A., Ejaz S. A., Channar P. A., Saeed A., ...More

JOURNAL OF MOLECULAR STRUCTURE, vol.1265, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1265
  • Publication Date: 2022
  • Doi Number: 10.1016/j.molstruc.2022.133350
  • Journal Name: JOURNAL OF MOLECULAR STRUCTURE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Keywords: oxidase B inhibition, Molecular docking, Hirshfeld surface, Carboxylate, MONOAMINE-OXIDASE, DERIVATIVES, INHIBITORS, ISOFORMS, ANALOGS
  • Hacettepe University Affiliated: Yes

Abstract

The current research outlines the synthesis of benzyl 4- (4-chlorophenylamino) -1-(4-chlorophenyl) -2,6bis(4-chlorophenyl) -1,2,5,6-tetrahydropyridine -3-carboxylate. The title compound was crystallized in the monoclinic space group P21/n with Z = 4 and unit cell parameters a = 13.6684 A (8), b = 9.1256 A (4), c = 14.0839 A (8), = 111.168 (7) degrees, and V = 1638.18 (17) degrees. The six-membered non-planar ring is shaped like a boat. Intermolecular C-H middotmiddotmiddotCl hydrogen bonds connect molecules in a three-dimensional crystal framework. The most significant contributions to crystal packing, according to the Hirshfeld surface investigation of the crystal structure, are from H middotmiddotmiddot H (35.3%), H... Cl/Cl... H (27.0%), and H middotmiddotmiddot C/C middotmiddotmiddot H (21.8%). As a result, van der Waals interactions take precedence in crystal packing. In-vitro studies suggested this compound has better IC 50 value of 0.588 +/- 0.09 mu M against MAO-A. In silico investigations, such as molecular docking, demonstrated that this molecule possessed exceptionally high Monoamine Oxidase A and Monoamine Oxidase B activity, with a binding energy value of -32.504 kJ/mol. Furthermore, Density functional theory (DFT) analyses supported these findings and suggested derivative 4 as a potential 'lead' molecule in pharmaceutical discovery and development.(c) 2022 Elsevier B.V. All rights reserved.